Epilim Chrono 200mg Prolonged Release Tablets
*Company:
SANOFIStatus:
No Recent UpdateLegal Category:
Product subject to medical prescription which may be renewed (B)Active Ingredient(s):
This medicinal product is subject to additional monitoring.
*Additional information is available within the SPC or upon request to the company
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Epilim IE Annual Risk Acknowledgement Form (v3.0).pdf
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EPILIM RMP Pharmacy Shelf Barker - (v3.0).pdf
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Updated on 08 August 2024
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1.3.1 Epilim Chrono 200mg SmPC IE.pdf
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
Legal category:Product subject to medical prescription which may be renewed (B)
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Epilim 2023 Patient Male Guide_02.pdf
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Updated on 26 July 2024
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1.3.1 Epilim Chrono Leaflet Text IE.pdf
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- Change to Section 1 - what the product is
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HPC Guide.pdf
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Interactive female patient guide- Epilim aRMM - June 2024.pdf
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Epilim Ireland ARAF Interactive Form_2.0.pdf
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F15-126601 Sanofi Epilim 2023 Patient Male Guide_12.pdf
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Epilim Ire - Valproate Pharmacy Sticker_MAT-IE-2000127.pdf
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Epilim Ire - Male Patient Guide_MAT-IE-2400026.pdf
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Epilim Ire - Patient Card _MAT-IE-2400024.pdf
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Epilim Ire - Female Patient Guide_MAT-IE-2000324.pdf
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Epilim Ire - Pharmacy Poster_MAT-IE-2000122.pdf
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Epilim Ire - HCP Guide_MAT-IE-2000323.pdf
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Updated on 02 April 2024
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1.3.1 Epilim Chrono 200mg SmPC IE (2).pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 02 April 2024
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1.3.1 Epilim Chrono Leaflet Text IE.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
Updated on 17 January 2024
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1.3.1 Epilim Chrono 200mg SmPC IE (1).pdf
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 10 November 2023
File name
1.3.1 Epilim Chrono 200mg SmPC IE.pdf
Reasons for updating
- Change to section 5.3 - Preclinical safety data
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 10 November 2023
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1.3.1 Epilim Chrono 200mg SmPC IE.pdf
Reasons for updating
- Change to section 5.3 - Preclinical safety data
Legal category:Product subject to medical prescription which may be renewed (B)
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Epilim Ire - Valproate Patient Guide IE.pdf
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Epilim Valproate Patient Booklet_4.0.pdf
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Updated on 03 March 2023
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1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg (4).pdf
Reasons for updating
- Change to section 2 - interactions with other medicines, food or drink
Updated on 03 March 2023
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1.3.1 SPC Epilim Chrono 200mg (1).pdf
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 01 March 2023
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1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg (2).pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
Updated on 01 March 2023
File name
1.3.1 SPC Epilim Chrono 200mg.pdf
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 10 August 2022
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1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg (2).pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
Updated on 10 August 2022
File name
1.3.1 SPC Epilim Chrono 200mg (2).pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
Legal category:Product subject to medical prescription which may be renewed (B)
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Epilim Valproate Patient Booklet_4.0.pdf
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Epilim Ireland ARAF Interactive Form_2.0.pdf
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Epilim A4 Pharmacy Poster_3.0.pdf
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Epilim Valproate HCP Booklet_3.0.pdf
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Epilim Shelf Barker_02.pdf
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Updated on 11 February 2022
File name
1.3.1 SPC Epilim Chrono 200mg.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.6 - Pregnancy and lactation
- Change to section 5.3 - Preclinical safety data
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 11 February 2022
File name
1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
Updated on 07 February 2022
File name
1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg (1).pdf
Reasons for updating
- Change to Section 1 - what the product is
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
- Change to section 3 - dose and frequency
- Change to section 3 - use in children/adolescents
- Change to section 3 - how to take/use
- Change to section 3 - duration of treatment
- Change to section 3 - overdose, missed or forgotten doses
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
Updated on 20 December 2021
File name
1.3.1 Package Leaflet Epilim Chrono.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
Updated on 17 December 2021
File name
1.3.1 SPC Epilim Chrono 200mg (1).pdf
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.4 - Special warnings and precautions for use
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 15 October 2021
File name
1.3.1 SPC Epilim Chrono 200mg IE1267S21.018.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 15 October 2021
File name
1.3.1 SPC Epilim EC 200mg Tablets IE1267 S21.018.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 15 October 2021
File name
1.3.1 Package Leaflet Epilim Chrono IE1267 S21.018.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
Updated on 22 September 2021
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1.3.1 Package Leaflet Epilim Chrono IE1273 EOP.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
Updated on 22 September 2021
File name
1.3.1 SPC Epilim Chrono 200mg IE1273 EOP.pdf
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 02 March 2021
File name
1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg.pdf
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
Updated on 02 March 2021
File name
1.3.1 SPC Epilim Chrono 200mg.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.8 - Undesirable effects
- Change to section 5.2 - Pharmacokinetic properties
Legal category:Product subject to medical prescription which may be renewed (B)
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Epilim RMP Pharmacy Poster.pdf
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MAT-IE-2001844(v1.0) Epilim Ireland ARAF Interactive.pdf
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Epilim Patient Booklet_Final_LR MAT-IE-2000324(v3.0).pdf
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Epilim Patient Guide MAT-IE-2000324(v3.0).pdf
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Epilim Patient Guide MAT-IE-2000324(v2.0).pdf
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Epilim HCP Guide MAT-IE-2000323(v2.0).pdf
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Updated on 06 July 2020
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1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg IE993 .pdf
Reasons for updating
- Previous version of PIL reinstated
Updated on 06 July 2020
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1.3.1 SPC Epilim Chrono 200mg IE993-IE994.pdf
Reasons for updating
- Correction of spelling/typing errors
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 06 July 2020
File name
1.3.1 SPC Epilim Chrono 200mg IE993-IE994.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
Updated on 02 April 2020
File name
1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg IE993 .pdf
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
- Change to section 5.3 - Preclinical safety data
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Section 4.6
Pregnancy Exposure Risk related to valproate
Both valproate monotherapy and valproate polytherapy including other antiepileptics, are frequently associated with abnormal pregnancy outcomes. Available data suggest that antiepileptic polytherapy including valproate is associated with a greater risk of congenital malformations than valproate monotherapy. Valproate was shown to cross the placental barrier both in animal species and in humans (see section 5.2).
In animals: teratogenic effects have been demonstrated in mice, rats and rabbits (see section 5.3).
Congenital malformations
There are limited data on the long term outcomes.
Available data from a population based study show that children exposed to valproate in utero are at increased risk of autistic spectrum disorder (approximately 3-fold) and childhood autism (approximately 5-fold) compared to the unexposed population in the study.
Available data from another population based study show that children exposed to valproate in utero are at increased risk of developing attention deficit/hyperactivity disorder (ADHD) (approximately 1.5 fold) compared to the unexposed population in the study.
If a Woman plans a Pregnancy
5.3 Preclinical Safety Data
Animal studies show that in utero exposure to valproate results in morphological and functional alterations of the auditory system in rats and mice.
Carcinogenesis, mutagenesis
Valproate was not mutagenic in bacteria (Ames test), or mouse lymphoma L5178Y cells at thymidine kinase locus (mouse lymphoma assay) and did not induce DNA repair activity in primary culture of rat hepatocytes. In in vivo studies, when tested at teratogenic doses, results were contradictory depending on the route of administration. After oral administration, the main route of administration in humans, valproate did not induce either chromosome aberrations in rat bone marrow, or dominant lethal effects in mice.
After intraperitoneal exposure to valproate, increased incidences of DNA and chromosome damage (DNA strand-breaks, chromosomal aberrations or micronuclei) have been reported in rodents. However, the relevance of the results obtained with the intraperitoneal route of administration is unknown.
Statistically significant higher incidences of sister-chromatid exchange (SCE) have been observed in epileptic patients exposed to valproate as compared to healthy subjects not exposed to valproate. However, there are confounding factors and contradictory results in 2 published studies. The biological significance of an increase in SCE frequency is not known.
Non-clinical data reveal no carcinogenicity hazard for humans based on conventional carcinogenicity studies.
Reproductive toxicology
Teratogenic effects (malformations of multiple organ systems) have been demonstrated in mice, rats, and rabbits.
In published literature, behavioural abnormalities have been reported in first generation offspring of mice and rats after in utero exposure. In mice, behavioural changes have also been observed in the 2nd and 3rd generations, albeit less pronounced in the 3rd generation, following an acute in utero exposure of the first generation to teratogenic doses. The underlying mechanisms of action and the relevance of these findings for humans are unknown.
Updated on 02 April 2020
File name
1.3.1 Package Leaflet Epilim Chrono 200, 300, 500mg IE993 .pdf
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
Updated on 17 March 2020
File name
1.3.1 epiim chrono pl IE729 766982.pdf
Reasons for updating
- Change to other sources of information section
Free text change information supplied by the pharmaceutical company
Addition of QR Code
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Valproate_Epilim_Annual Risk acknowledgement form_final-2205036-15052018124629-636619851950937500.pdf
Reasons for updating
- Replace File
Updated on 09 December 2019
File name
Epilim Chrono 200mg SmPC.pdf
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
- Change to section 5.2 - Pharmacokinetic properties
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 09 December 2019
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Epilim Chrono 200, 300, 500mg PIL.pdf
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
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DHPC for Pharmacists_April_2018_approved-2205036-17042018172152-636595825230312500.pdf
Reasons for updating
- Add New Doc
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DHPC for Prescribers_April 2018_approved-2205036-17042018172612-636595827803125000.pdf
Reasons for updating
- Add New Doc
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Valproate _Epilim_Pharmacy Shelf Barker_final-2205036-15052018124936-636619853810312500.pdf
Reasons for updating
- Add New Doc
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Valproate HCP Booklet_2018-05-2205036-20062018101407-636650864482115000.pdf
Reasons for updating
- Add New Doc
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Valproate_Epilim_ A4 Pharmacy Poster_final-2205036-15052018124904-636619853514531250.pdf
Reasons for updating
- Add New Doc
File name
Valproate_Epilim_Annual Risk acknowledgement form_final-2205036-15052018124629-636619851950937500.pdf
Reasons for updating
- Add New Doc
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Valproate Patient Booklet_final_reformatted_19.06.2018-2205036-20062018090312-636650821952427500.pdf
Reasons for updating
- Add New Doc
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Valproate_Epilim_Patient Card_final-2205036-15052018124823-636619853060468750.pdf
Reasons for updating
- Add New Doc
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Pharmacy warning sticker-2205036-17042018170547-636595815700937500.pdf
Reasons for updating
- Add New Doc
Updated on 18 April 2019
File name
PIL Epilim Chrono 200, 300, 500mg IE682 IE656.pdf
Reasons for updating
- Change to section 4 - possible side effects
Updated on 18 April 2019
File name
SPC Epilim Chrono 200mg IE656 IE682.pdf
Reasons for updating
- Change to section 4.8 - Undesirable effects
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.8 Undesirable Effects
Nervous system disorders:
Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder, diplopia.
Renal and urinary disorders:
Common: urinary incontinence
Updated on 23 October 2018
File name
PIL epilim chrono 200, 300, 500mg prolonged release tablets .pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
Updated on 18 October 2018
File name
spc epilim chrono 200mg prolonged release tablets.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 5.2 - Pharmacokinetic properties
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Even if she has amenorrhea she must follow all the advice on effective contraception.
Estrogen-containing products
Concomitant use with estrogen-containing products, including estrogen-containing
hormonal contraceptives, may potentially result in decreased valproate efficacy (see section 4.5). Prescribers should monitor clinical response (seizure control or mood control) when initiating or discontinuing estrogen-containing products.
On the opposite, valproate does not reduce efficacy of hormonal contraceptives.
Annual treatment reviews by a specialist
Co-administration of valproate and quetiapine may increase the risk of neutropenia/leucopenia.
Estrogen-containing products, including estrogen-containing hormonal contraceptives
Estrogens are inducers of the UDP-glucuronosyl transferase (UGT) isoforms involved in valproate glucuronidation and may increase the clearance of valproate, which would result in decreased serum concentration of valproate and potentially decreased valproate efficacy (see section 4.4). Consider monitoring of valproate serum levels.
On the opposite, valproate has no enzyme inducing effect; as a consequence, valproate
does not reduce efficacy of oestroprogestative agents in women receiving hormonal contraception.
Epilim usually has no enzyme-inducing effect; as a consequence, Epilim does not reduce the efficacy of oestroprogestative agents in women receiving hormonal contraception, including the oral contraceptive pill.
4.6 Fertility, Pregnancy and Lactation
However the available evidence does not suggest it prevents the birth defects or malformations due to valproate exposure.
Women of childbearing potential
Estrogen-containing products
Estrogen-containing products, including estrogen-containing hormonal contraceptives, may increase the clearance of valproate, which would result in decreased serum concentration of valproate and potentially decreased valproate efficacy (sections 4.4 and 4.5).
Risk in the neonate
The pharmacological (or therapeutic) effects of Epilim Chrono may not be clearly correlated with the total or free (unbound) plasma valproic acid levels.
Metabolism
The major pathway of valproate biotransformation is glucuronidation (~40%), mainly via UGT1A6, UGT1A9, and UGT2B7.
Epilim Chrono formulations are prolonged release formulations which demonstrate in pharmacokinetic studies less fluctuation in plasma concentration compared with other established conventional and prolonged release Epilim formulations.
Updated on 21 September 2018
File name
Epilm.pdf
Reasons for updating
- Correction of spelling/typing errors
Updated on 16 August 2018
File name
1.3.1 Leaflet PA54015002-3 EC 200,500mg.pdf
Reasons for updating
- Change to section 6 - what the product contains
- Change to section 6 - what the product looks like and pack contents
- Change to section 6 - marketing authorisation holder
- Change to section 6 - manufacturer
Updated on 16 August 2018
File name
1.3.1 SPC PA54015010 Chrono 200mg.pdf
Reasons for updating
- Change to section 6.5 - Nature and contents of container
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Srction 6.5
. Pack sizes of 30 or 100 tablets with 10 tablets per strip and 112 tablets.
Updated on 02 August 2018
File name
1.3.1 Leaflet EC 200,500mg.pdf
Reasons for updating
- Change to Section 1 - what the product is
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
- Change to section 3 - dose and frequency
- Change to section 3 - use in children/adolescents
- Change to section 3 - how to take/use
- Change to section 3 - duration of treatment
- Change to section 3 - overdose, missed or forgotten doses
Updated on 02 August 2018
File name
1.3.1 SPC Chrono 200mg 5415010.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.6 - Pregnancy and lactation
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
directly impacts on SmPC sections 4.2, 4.3, 4.4 and 4.6, but there’s also minor QRD editorial updates to 4.5, 4.8, 4.9 and 5.2 that the HPRA requested
Updated on 29 November 2017
File name
PIL_9113_86.pdf
Reasons for updating
- New PIL for new product
Updated on 29 November 2017
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 2 - excipient warnings
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
Updated on 15 August 2017
Reasons for updating
- New SPC for new product
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 15 August 2017
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Section 4.5 interactions – this has been added
- Nimodipine
In patients concomitantly treated with sodium valproate and nimodipine the exposure to nimodipine can be increased by 50%. The nimodipine dose should therefore be decreased in case of hypotension
Updated on 21 July 2017
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Updated on 02 June 2017
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Updated on 04 November 2016
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Updated on 03 November 2016
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 6 - date of revision
Updated on 13 May 2015
Reasons for updating
- Addition of black triangle
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Section 4.2: new paragraph 'Female children, female adolescents, women of childbearing potential and pregnant women'.
Section 4.3: new paragraph added regarding mitrochondrial disorders.
Section 4.4: new boxed wording titled 'Female children, female adolescents, women of childbearing potential and pregnant women'.
Paragraph title 'Women of childbearing potential' has been removed.
New information on 'Patients with known or suspected mitrochondrial disease' included.
Section 4.6: Majority of section has been updated with new paragraphs title 'Breastfeeding' and 'Fertility' added.
Section 4.8: 'Congenital malformations and development disorders' added.
Updated on 01 May 2015
Reasons for updating
- Change to information about pregnancy or lactation
- Addition of black triangle
- Change to warnings or special precautions for use
Updated on 22 December 2014
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Patients with an underlying carnitine palmitoyltransferase (CPT) type II deficiency should be warned of the greater risk of rhabdomyolysis when taking valproate.
Section 4.5: 4.5.3 updated to include:
Co-administration of valproate and quetiapine may increase the risk of neutropenia/leucopenia.
Section 4.6: 4.6.1 paragraph 'Risks associated with Epilim' updated:
In humans: Available data suggest an increased incidence of minor or major malformations including neural tube defects, craniofacial defects, malformation of the limbs, cardiovascular malformations and multiple anomalies involving various body systems in offspring born to mothers with epilepsy treated with valproate when compared to the incidence for certain other antiepileptic drugs. Data from a meta-analysis (including registries and cohort studies) has shown an incidence of congenital malformations in children born to epileptic women exposed to valproate monotherapy during pregnancy at 10.73% (95% CI: 8.16 – 13.29). Available data indicate dose dependency of this effect.
'Risks in the neonate' updated:
Very rare cases of haemorrhagic syndrome have been reported in neonates whose mothers have taken valproate during pregnancy. This haemorrhagic syndrome is related to thrombocytopenia, hypofibrinogenemia and/or to decreases in other coagulation factors; afibrinogenemia has also been reported and may be fatal. These are possibly associated with a decrease of coagulation factors. However, this syndrome has to be distinguished from the decrease of the vitamin-K factors induced by phenobarbital and other anti-epileptic enzyme inducing drugs.
Therefore, platelet count, fibrinogen plasma level, coagulation tests and coagulation factors should be investigated in neonates.
Cases of hypoglycaemia have been reported in neonates whose mothers have taken valproate during the third trimester of pregnancy.
Cases of hypothyroidism have been reported in neonates whose mothers have taken valproate during pregnancy.
Withdrawal syndrome (such as, in particular, agitation, irritability, hyper-excitability, jitteriness, hyperkinesia, tonicity disorders, tremor, convulsions and feeding disorders) may occur in neonates whose mothers have taken valproate during the last trimester of pregnancy.
Section 4.8: updated as follows:
The following CIOMS frequency rating is used, when applicable:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data).
Congenital, familial and genetic disorders: (see section 4.6. Fertility, Ppregnancy and Llactation)
Hepatobiliary disorders:
Common: rare cases of liver injury (see section 4.4. Special warnings and precautions for use)
Gastrointestinal disorders:
Very common: (nausea,
Common: vomiting, gingival disorder (mainly gingival hyperplasia), stomatitis. abdominal pain upper, diarrhoea)
The above three adverse events frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment. These problems can usually be overcome by taking Epilim with or after food or by using Enteric Coated Epilim.
Uncommon: Very rare cases of pancreatitis, sometimes lethal, have been reported (see section 4.4 Special Warnings and Special Precautions for Use).
Nervous system disorders:
Very common: tremor
Common: extrapyramidal disorder, stupor*, somnolence, convulsion*, memory impairment, headache, nystagmus,
Uncommon: coma*, encephalopathy, lethargy* (see below), reversible parkinsonism, ataxia, paresthesia.
Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder.
Sedation has been reported occasionally, usually when in combination with other anticonvulsants. In monotherapy it occurred early in treatment on rare occasions and is usually transient.
*Rare cases of lethargy and confusion, occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed. These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anticonvulsants, notably phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage. Extrapyramidal disorders.
Very rare cases of reversible dementia associated with reversible cerebral atrophy have been reported.
Ataxia and transient and/or dose related fine postural tremor have occasionally been reported.
Extrapyramidal disorder which may not be reversible, including reversible Parkinsonism.
Cognitive disorders.
An increase in alertness may occur; this is generally beneficial but occasionally aggression, hyperactivity and behavioural disorders have been reported.
Cases of isolated and moderate hyperammonaemia without change in liver function may occur frequently and should not cause treatment discontinuation. However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness. Should these symptoms occur Epilim should be discontinued.
Hyperammonaemia associated with neurological symptoms has also been reported (see section 4.4.2 Precautions). In such cases further investigations should be considered.
Metabolic and nutrition disorders:
Common: hyponatraemia.
Rare: hyperammonaemia* (see section 4.4.2 Precautions)
*Cases of isolated and moderate hyperammonaemia without change in liver function may occur frequently and should not cause treatment discontinuation. However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness. Should these symptoms occur Epilim should be discontinued.
Hyperammonaemia associated with neurological symptoms has also been reported (see section 4.4.2 Precautions). In such cases further investigations should be considered.
Very rare cases of hyponatremia have been reported.
Syndrome of Inappropriate Secretion of ADH (SIADH)
Endocrine Disorders:
Uncommon: Syndrome of Inappropriate Secretion of ADH (SIADH), hyperandrogenism (hirsutism, virilism, acne, male pattern alopecia, and/or androgen increased)
Rare: hypothyroidism (see section 4.6 Fertility, pregnancy and lactation)
Blood and lymphatic system disorders:
Frequent occurrence of Common: anaemia, thrombocytopenia, rare cases of anaemia, leucopoenia or (see section 4.4.2 Precautions).
Uncommon: pancytopenia., leucopenia.
The blood picture returned to normal when the drug was discontinued.
Rare: Bbone marrow failure, including pure red cell aplasia., Aagranulocytosis, anaemia macrocytic, macrocytosis.
Isolated finding of a reduction in blood fibrinogen and/or increase in prothrombin time have been reported, usually without associated clinical signs and particularly with high doses (Epilim has an inhibitory effect on the second phase of platelet aggregation). Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations (see also section 4.6 Fertility, Ppregnancy and Llactation).
Deficiency in Factor VIII / Von Willebrand.
Skin and subcutaneous tissue disorders:
Very rare: toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme, rash.
Common: hypersensitivity, Ttransient and/or dose related alopecia., has often been reported. Regrowth normally begins within six months, although the hair may become more curly than previously.
Uncommon: angioedema, rash, hair disorder (such as hair texture abnormal, hair colour changes, hair growth abnormal)
Rare: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.
Musculoskeletal and connective tissue disorders:
Uncommon: There have been reports of decreased bone mineral density decreased, osteopenia, osteoporosis and fractures in patients on long-term therapy with Epilim. The mechanism by which Epilim affects bone metabolism has not been identified.
Rare: systemic lupus erythematosus (see section 4.4.2 Precautions), rhabdomyolysis (see section 4.4.2 Precautions)
Reproductive system and breast disorders:
Common: dysmenorrhea
Uncommon: amenorrhea
Rare: male infertility, polycystic ovaries
Amenorrhoea and dysmenorrhea have been reported.
Very rarely gynaecomastia has occurred.
Male infertility.
Vascular disorders:
Common: haemorrhage (see section 4.4.2 Precautions and 4.6 Fertility, pregnancy and lactation).
Uncommon: The occurrence of vasculitis has occasionally been reported.
Ear and labyrinth disorders:
Common: Deafness, either reversible or irreversible has been reported rarely.
Renal and urinary disorders:
Uncommon: renal failure
There have been isolated reports of a reversible Fanconi’s syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria) but the mode of action is as yet unclear.
Very rRare: cases of enuresis, tubulointerstitial nephritishave been reported.
reversible Fanconi syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria) associated with Epilim therapy, but the mode of action is as yet unclear.
Immune system disorders:
Angioedema, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.
Allergic reactions (ranging from rash to hypersensitivity reactions) have been reported.
Psychiatric disorders:
Common: Cconfusional state, hallucinations, aggression*, agitation*, disturbance in attention*
Rare: abnormal behaviour*, psychomotor hyperactivity*, learning disorder*
*These ADRs are principally observed in the paediatric population.
General disorders and administration site conditions:
Very rare cases of Uncommon: hypothermia, non-severe peripheral oedema peripheral have been reported.
Increase in weight may also occur. Since it is a risk factor for polycystic ovary syndrome, it should be carefully monitored (see section 4.4 Special Warnings and Special Precautions for Use).
Respiratory, thoracic and mediastinal disorders:
Uncommon: pleural effusion
Investigations:
Common: Weight increased*
Rare: Coagulation factors decreased (at least one), abnormal coagulation tests (such as prothrombin time prolonged, activated partial thromboplastin time prolonged, thrombin time prolonged, INR prolonged), biotin deficiency/biotinidase deficiency.
*Weight increase should be carefully monitored since it is a factor for polycystic ovary syndrome (see section 4.4.2 Precautions)
Neoplasms benign, malignant and unspecified (including cysts and polyps):
Rare: myelodysplastic syndrome
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via IMB HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpraimb.ie; e-mail: imbpharmacovigilance@imb.iemedsafety@hpra.ie.
Section 4.9: updated as follows:
Signs of massive overdose, i.e. plasma concentration 10 to 20 times maximum therapeutic levels, usually include CNS depression or coma with muscular hypotonia, hyporeflexia, miosis, impaired respiratory function, metabolic acidosis, hypotension and circulatory collapse/shock.
Deaths have occurred following massive overdose; nevertheless, a favourable outcome is usual.
Symptoms may however be variable and seizures have been reported in the presence of very high plasma levels (see also section 5.2 Pharmacokinetic Properties). Cases of intracranial hypertension related to cerebral oedema have been reported.
The presence of sodium content in the valproate formulations may lead to hypernatraemia when taken in overdose.
Updated on 06 November 2013
Reasons for updating
- Change to side-effects
Updated on 01 November 2013
Reasons for updating
- Change to section 4.8 - Undesirable effects
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Updated on 24 August 2012
Reasons for updating
- Change to section 7 - Marketing authorisation holder
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Updated on 13 April 2012
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
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- Extrapyramidal disorders
- Interactions with Lamotrigine
- Interactions with Felbamate
- Male infertility
- Peadiatric data in Bipolar Disorder
- Alcohol intake
- Use of contraception in women
Updated on 21 March 2012
Reasons for updating
- Change to information about pregnancy or lactation
- Change to drug interactions
- Change to information about drinking alcohol
Updated on 31 May 2011
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
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Updated on 02 February 2011
Reasons for updating
- Changes to therapeutic indications
Updated on 04 October 2010
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Updated on 16 October 2009
Reasons for updating
- Change due to user-testing of patient information
Updated on 08 October 2009
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
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Additional adverse events to section 4.8
Addition of rifampicin and topiramate to section 4.5
Modification of section 4.9
Updated on 05 January 2009
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
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Updated on 05 January 2009
Reasons for updating
- Change to warnings or special precautions for use
Updated on 24 July 2008
Reasons for updating
- Change to, or new use for medicine
Updated on 18 July 2008
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
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Updated on 18 July 2008
Reasons for updating
- Change to marketing authorisation holder
Updated on 04 July 2008
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 10 - Date of revision of the text
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Updated on 06 May 2008
Reasons for updating
- Change to section 10 - Date of revision of the text
- Improved electronic presentation
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Updated on 08 August 2007
Reasons for updating
- Improved electronic presentation
Updated on 18 December 2006
Reasons for updating
- Improved electronic presentation
Updated on 06 May 2006
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 04 January 2006
Reasons for updating
- Change to section 1 - Name of medicinal product
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 6.1 - List of excipients
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 04 January 2006
Reasons for updating
- Improved electronic presentation
Updated on 29 October 2004
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
- Change to section 10 - Date of revision of the text
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Updated on 13 October 2004
Reasons for updating
- New PIL for medicines.ie
Updated on 04 August 2004
Reasons for updating
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 26 June 2003
Reasons for updating
- New SPC for medicines.ie
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